Data driven framework for optimizing artificial organ printing and scaffold selection for regenerative medicine

ABSTRACT

A method for generating a personalized scaffold for an individual includes acquiring images of an anatomy of interest corresponding to an intended scaffold location and acquiring test results related to the anatomy of interest. One or more functional specifications are generated based on the images and test results and one or more scaffold parameters are selected based on the functional specifications. A final scaffold may then be generated using the one or more scaffold parameters.

TECHNICAL FIELD

The present disclosure relates to a framework for optimizing artificialorgan printing and scaffold selection for regenerative medicine. Thetechniques described herein may be applied, for example, to the printingof organs and/or scaffolding related to, for example, artificial limbs,heart, valves, vasculature, kidney, lungs, liver, prostate, bladder,ovaries, eye, and skin.

BACKGROUND

Many diseases are currently treated with replacement or repair of theaffected anatomy. In most cases, a device is implanted to mimic themorphology and function of the original anatomy. For example, bare metaland drug eluting stents are used for the treatment of coronary arterydisease, scaffolds are used for treating aortic aneurisms, andartificial aortic valves are used for valve replacements. However mostof the devices suffer from the lack of bio-compatibility andpersonalization. As most replacement devices are based on metal partsfor structural integrity (e.g., coronary stents) they incite immuneresponses. In addition, current devices come only in a discrete set ofoptions, mostly to reduce development and manufacturing cost. Forexample, aortic valve replacement devices are usually available in threeoptions which vary in size (e.g., with 3 mm gaps between models). Thus,there is a significant lack of personalization as the anatomy of thepatient can exhibit a large variety of distinct shapes which are notpossible to capture with a limited number of discrete device options.

Accordingly, a more personalized device creation approach is desired inclinical practice. Expectations are that personalized devices canimprove current procedural outcomes. In the case of complex anatomicaldeformations, such as in pediatric cases, a personalized model may bethe only viable option.

SUMMARY

Embodiments of the present invention address and overcome one or more ofthe above shortcomings and drawbacks, by providing methods, systems, andapparatuses related to a data driven framework that may be applied toorgan printing and scaffold selection for regenerative medicineapplications. The disclosed techniques enable morphological modeling ofthe affected anatomy and subsequent design of the optimal organ modelusing a computational model. Instead of optimizing only thecomputational model in respect to its parameters, the printerspecifications are incorporated in the optimization procedure. The finalmodel can be printed using 3D bio-printers and used directly for organreplacement. The disclosed techniques also enable morphological modelingof the affected anatomy and subsequent design of the optimal scaffold.The final scaffold design can be manufactured (e.g., using 3D printers)and used either directly or as a mold for scaffolds requiring specificmaterials that cannot be printed.

According to some embodiments, a method for generating a personalizedscaffold for an individual includes acquiring images of an anatomy ofinterest corresponding to an intended scaffold location and acquiringtest results related to the anatomy of interest. One or more functionalspecifications are generated based on the images and test results. Insome embodiments of the aforementioned method, the functionalspecifications comprise one or more computational model parameters.These computational model parameters may include, for example, anindication of geometrical features and/or mechanical properties of theanatomy of interest. The functional specifications may also (oralternatively) comprise one or more clinical parameters. These clinicalparameters may include, for example, one or more of a diameter, ejectionfraction, flow, or volume corresponding to the anatomy of interest. Oncethe functional specifications are generated, they may be used to selectone or more scaffold parameters. In some embodiments of theaforementioned method, the scaffold parameters are selected based on theone or more functional specifications by selecting an initial set ofscaffold parameters from a database based on the functionalspecifications and then optimizing the initial set of scaffoldparameters using a functional computational model to yield thefunctional specifications. Once the scaffold parameters are selected,they may be used to generate a final scaffold.

Various techniques may be applied to generate the final scaffold in theaforementioned method. In some embodiments, the final scaffold isgenerated using an additive manufacturing process. This additivemanufacturing process may include, for example, the generation of astereolithography (STL) tetrahedral model with material properties foreach tetrahedral corresponding to the scaffold parameters. In otherembodiments, the final scaffold is generated by creating a mold based onthe one or more scaffold parameters and using the mold to grow the finalscaffold. In other embodiments, the scaffold parameters comprise a setof optimal printer parameters the final scaffold is generated byidentifying a mapping function which describes a relationship betweenthe one or more functional specifications and printer parameterscorresponding to a three-dimensional printer and selecting one or moredesired output characteristics. The set of optimal printer parametersare generated by optimizing the mapping function according to the one ormore desired output characteristics. Then, the three-dimensional printermay be used to print a personalized organ according to the set ofoptimal printer parameters.

According to other embodiments of the present invention, a method forgenerating a personalized organ model for an individual includesacquiring images of an anatomy of interest corresponding to an organ andacquiring test results related to the anatomy of interest. One or morecurrent functional specifications (e.g., computational model parametersand/or clinical parameters) are determined based on the images and testresults. Then, a mapping function is identified which describes arelationship between the one or more current functional specificationsand printer parameters corresponding to a three-dimensional bio-printer.Desired output characteristics are selected and a set of optimal printerparameters are generated by optimizing the mapping function according tothe one or more desired output characteristics. The three-dimensionalbio-printer may then be used to print a personalized organ replacementaccording to the set of optimal printer parameters.

According to other embodiments, a system for generating a personalizedregenerative medicine device (e.g., replacement organ) includes animaging device, a processing computer, and a three-dimensional printer(e.g., a bio-printer). The imaging device is configured to acquireimages of an anatomy of interest corresponding to an intended usagelocation of the personalized regenerative medicine device. Theprocessing computer is configured to receive the images of the anatomyof interest from the imaging device, acquire test results related to theanatomy of interest, generate one or more functional specificationsbased on the images and test results, and determining one or moreprinter parameters based on the one or more functional specifications.In some embodiments, the printer parameters comprise a set of optimalprinter parameters determined by identifying a mapping function whichdescribes a relationship between the functional specifications andavailable printer parameters corresponding to the three-dimensionalprinter. One or more desired output characteristics are selected and theset of optimal printer parameters are generated by optimizing themapping function according to the one or more desired outputcharacteristics. The three-dimensional printer in the aforementionedsystem is configured to generate the personalized regenerative medicinedevice using the one or more printer parameters.

Additional features and advantages of the invention will be madeapparent from the following detailed description of illustrativeembodiments that proceeds with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other aspects of the present invention are bestunderstood from the following detailed description when read inconnection with the accompanying drawings. For the purpose ofillustrating the invention, there is shown in the drawings embodimentsthat are presently preferred, it being understood, however, that theinvention is not limited to the specific instrumentalities disclosed.Included in the drawings are the following Figures:

FIG. 1 illustrates a system for optimizing artificial organ printing andscaffold selection for regenerative medicine, according to someembodiments of the present invention;

FIG. 2 provides an example process for manufacturing an anatomicalorgan, according to some embodiments of the present invention;

FIG. 3 provides an example process for manufacturing a patient-specificscaffold, according to some embodiments; and

FIG. 4 illustrates an exemplary computing environment within whichembodiments of the invention may be implemented.

DETAILED DESCRIPTION

The following disclosure describes the present invention according toseveral embodiments directed at methods, systems, and apparatusesrelated to processing medical images and clinical patent data to providepersonalized structures and engineered tissues for use in regenerativemedicine applications. For example, in some embodiments, the techniquesdescribed herein may be used to create a personalized “scaffold.” Theterm scaffold, as used herein, refers to an artificial structure onwhich tissue growth cells may be implanted or ‘seeded’ to supportthree-dimensional tissue formation. Thus, a scaffold may be used to growtissues in order to replace or repair diseased organs and anatomy. Inother embodiments, an optimized and personalized organ model isdeveloped with respect to a bio-printer. This model can be directlyprinted using the bio-printer and also used as a replacement for thediseased anatomy. The techniques described herein may be applied, forexample, to the creation of structures related to artificial limbs,heart, valves, vasculature, kidney, lungs, liver, prostate, bladder,ovaries, eye, and skin.

FIG. 1 illustrates a system 100 for optimizing artificial organ printingand scaffold selection for regenerative medicine, according to someembodiments of the present invention. An Imaging Device 105 is used toacquire one or more images of an anatomy of interest. In the example ofFIG. 1, a Magnetic Resonance Imaging (MR) scanner is shown. However, inother embodiments, other imaging devices generally known in the art maybe employed such as, without limitation, a Computed Tomography (CT)scanner, a Positron Emission Tomography (PET) scanner, or an ultrasounddevice. Additionally, in some embodiments, imaging data is acquiredusing multiple modalities and aggregated to provide various types ofimage data corresponding to the anatomy of interest.

A Processing Computer 120 receives the image data from the ImagingDevice 105 via a computer network 110. This computer network 110 may beconfigured using a variety of hardware platforms. For example, thecomputer network 110 may be implemented using the IEEE 802.3 (Ethernet)or IEEE 802.11 (wireless) networking technologies, either separately orin combination. In addition, the computer network 110 may be implementedwith a variety of communication tools including, for example, TCP/IPsuite of protocols. In some embodiments, the computer network 110 is theInternet. A virtual private network (VPN) may be used to extend aprivate network across the computer network 110. Image data received bythe Processing Computer 120 may be stored in a Database 125. ThisDatabase 125 may be implemented, for example, using a database packagesuch as Microsoft Access™ or a DBMS such as Microsoft SQL Server™, mySQLor postgreSQL.

The Processing Computer 120 is operably coupled to a User Interface 130which allows clinicians to provide in-vitro and in-vivo test results tothe Processing Computer 120. These test results may include, forexample, measurements related to the anatomy of interest such asdiameters, ejection fraction, flow, and volume. Based on the receivedimages and test results, one or more functional specifications aredeveloped. These functional specifications may include computationalmodel parameters (e.g., geometry, mechanical properties such as tissuestiffness, etc.), clinical parameters/measurements (e.g., diameters,ejection fraction, flow, volume) or any other parameters specifying theanatomy and function of the organ of interest.

Continuing with reference to FIG. 1, the Processing Computer 120 usesthe functional specifications to determine one or more parameterscorresponding to a Three-Dimensional Printer 115. The printer parametersare optimized using the functional specifications to produce an outputwith desired characteristics. In some embodiments, a mapping function isidentified which describes a relationship between the functionalspecifications and the printer parameters which are available on theThree-Dimensional Printer 115. The optimal printer parameters aregenerated by optimizing the mapping function according to the desiredcharacteristics. This process is described in greater detail below withrespect to FIG. 2.

Once generated the printer parameters generated by the ProcessingComputer 120 are sent to Three-Dimensional Printer 115 in order to printa regenerative medicine device. In some embodiments, the regenerativemedicine device is a scaffold on which living cells may grow areplacement organ for the individual. In these embodiments, theThree-Dimensional Printer 115 uses an “ink” comprised of living cellsand scaffolding material such as biodegradable polymers or collagen. Thescaffolding material provides a structure on which the cells will latergrow. As each layer is printed, it is solidified (e.g., using heat,chemicals, or ultraviolet light). This layer-by-layer process isreferred to as “additive manufacturing” because the finished scaffold ismade by adding material to build up a three-dimensional shape. In otherembodiments, the regenerative medicine device is a replacement organ andthe Three-Dimensional Printer 115 is a bio-printer. As is understood inthe art, a bio-printer uses additive manufacturing techniques to depositliving cell material in layers whose thickness depends on the tissuebeing printed. In some embodiments, the Three-Dimensional Printer 115provides hybrid functionality such that the same printer can be used forgenerating scaffolding and/or replacement organs.

Once the Three-Dimensional Printer 115 has completed printing the organ,the tissues are stored in an incubator referred to as a “bioreactor.”While in the bio-reactor, the tissues mature in preparation of use inthe patient's body. Additionally, tests may be performed while the organis in the bioreactor to confirm that it is able to perform as designed.It should be noted that, in some embodiments, a specialized bio-printermay be used to print directly in the patient's body. In this case, theprinted tissue can mature directly in the patient's body and incubationin the bioreactor can be omitted.

FIG. 2 provides an example process 200 for manufacturing an anatomicalorgan, according to some embodiments of the present invention. At step205, images of the anatomical area of interest (including the anatomicalorgan of interest) are acquired using one or more imaging devices (e.g.,Imaging Device 105 in FIG. 1). The image data may be acquired using anytechnique known in the art including, without limitation, acquisitiontechniques which employ CT, Ultrasound, and MRI imaging modalities. Datacan be temporal (i.e., acquired at different time stamps) ornon-temporal in nature. At step 210 the results of one or more in-vitroand in-vivo tests related to the anatomical organ of interest arereceived. The exact tests performed to generate the information receivedat step 210 will vary, for example, based on organ of interest and anydiseases or disorders present in that organ. For example, tests may beperformed on a valve to measure flow or volume.

Next, at step 215, the organ of interest is measured and modeled basedon the acquired data, resulting in functional specification v₀. Thefunctional specification v₀can represent computational model parameters(e.g., geometry, mechanical properties such as tissue stiffness,geometry, etc.), clinical parameters/measurements (e.g., diameters,ejection fraction, flow, volume) or any other parameters specifyinganatomy and function of the organ.

At step 220, the functional specification v₀, is used to determineparameters for a bio-printer capable of printing the organ. The outputof the bio-printer is a mapping function M from the input v₀, to thedesired characteristics of the output v₁whereby the printer iscontrolled by its settings p:

∥v ₁ −M(p,v ₀)∥<δ;δ≧0

where δ is an infinitesimal number and p are the printing parameters.These printing parameters vary according to the model and availablefeatures of the bio-printer. Examples of parameters that may be usedinclude, without limitation, nozzle diameter, pressure on material, andprint speed. In some embodiments, the available printing parameters arespecified in a range of values to simplify the identification of viableparameter combinations.

In some embodiments, an optimization approach is used to find optimizedprinting parameters p which minimize the deviation of the desired outputv₁ and the printer output, characterized by the mapping function M(p,v₀) with respect to the printer parameters p:

${O_{p}\text{(}v_{1}},{{M\left( {p,v_{0}} \right)} = {\min\limits_{p}{{v_{1} - {M\left( {p,v_{0}} \right)}}}}}$

Various techniques may be used for solving this equation including, forexample, techniques that employ gradient methods (e.g., gradientdescent). Finally, at step 225, the organ is printed with the optimalprinter parameters p. The printed organ may then be used as areplacement for the diseased organ or anatomy.

FIG. 3 provides an example process 300 for manufacturing apatient-specific scaffold, according to some embodiments. The process300 shown in FIG. 3 extends the general concepts presented in FIG. 2 tosituations where a scaffold for an organ, rather than the organ itself,is created using a three-dimensional printer. At step 305, images of theanatomy of interest (including the organ(s) of interest) are acquired.The image data may be acquired using any technique known in the artincluding, without limitation, techniques which employ CT, Ultrasound,and MRI imaging modalities. In some instances, the acquired data can betemporal (i.e., acquired at different time stamps). At step 310 theresults of one or more in-vitro and in-vivo tests related to theanatomical organ of interest are received. As with the example discussedabove with respect to FIG. 2, the exact information included in the testresults will vary according the anatomy and diseases being targeted.

Next, at step 315, the patient data acquired at step 305 is used tomeasure and model the organ of interest in order to generate afunctional specification v of the organ. The functional specification vcan represent computational model parameters (e.g., geometry, mechanicalproperties such as tissue stiffness, etc.), clinicalparameters/measurements (e.g., diameters, ejection fraction, flow,volume) or any other parameters specifying the anatomy and function ofthe organ. Some of these measurements may be made directly on the imagedata acquired at step 305. For example, the diameter of a valve may bemeasured in the image directly either manually or using automatictechniques generally known in the art. For more complex information, a3D model of the organ can be developed from the image data and/or testresults acquired at steps 305 and 310, again using any technique knownin the art. Using the model, organ structure and behavior can be morethoroughly analyzed in order to develop a more robust functionalspecification v for the organ.

Continuing with reference to FIG. 3, at step 320, the optimal scaffoldparameters s₀ which can be used for manufacturing are selected based onthe functional specification v. At 320, a correlation between v and s isdetermined based on pre-existing patient data (e.g., stored in adatabase). For example, v can represent geometry information of theideal scaffold. Thus, given a database of healthy patients where v isknown, a similar patient can be found based on the functionalspecifications v (e.g., using Euclidean distance or another appropriatesimilarity metric to compare v to database record.

At step 325, the specifications of the scaffold v are optimized based ona functional computational model. The computational model applied atstep 325 is a functional model and different scaffold parameter settingss can be explored in respect to their effect on the anatomical andfunctional properties of the anatomy or organ. The scaffold parameters sare a sub-set of all parameters of the computational models. Thecomputational model can help one to verify cheaply (without 3D printing)the effects of certain scaffold parameters s in respect to thefunctional specification v. For example, consider a patient that isclose to heart failure and requires a heart replacement. The goal may beto bring the Ejection Fraction to greater than 50% (so this would be thefunctional specification v). Now one of the parameters of thecomputational model (and scaffold) is the geometry. From N possiblechanges of the initial geometry the computational model could simulatethe effects on the Ejection Fraction and the best configuration would beused for the scaffold (or direct organ printing).

Finally, at step 330, scaffold manufacturing is performed. During thisstep the final scaffold is manufactured on which tissue will grow.Various techniques may be used to perform the manufacturing using thescaffold parameters s. For example, in some embodiments, additivemanufacturing using 3D printers is employed. This might involvegenerating a CAD stereolithography (STL) tetrahedral model with specificmaterial properties for each tetrahedral. In other embodiments, a moldis created to build the scaffold with specific material that cannot beprinted.

FIG. 4 illustrates an exemplary computing environment 400 within whichembodiments of the invention may be implemented. In some embodiments,the computing environment 400 may be used to implement one or more ofthe components illustrated in the system 100 of FIG. 1. For example,this computing environment 400 may be configured to execute theprocesses 200, 300 described above with respect to FIGS. 2 and 3,respectively. Computers and computing environments, such as computersystem 410 and computing environment 400, are known to those of skill inthe art and thus are described briefly here.

As shown in FIG. 4, the computer system 410 may include a communicationmechanism such as a bus 421 or other communication mechanism forcommunicating information within the computer system 410. The computersystem 410 further includes one or more processors 420 coupled with thebus 421 for processing the information. The processors 420 may includeone or more central processing units (CPUs), graphical processing units(GPUs), or any other processor known in the art.

The computer system 410 also includes a system memory 430 coupled to thebus 421 for storing information and instructions to be executed byprocessors 420. The system memory 430 may include computer readablestorage media in the form of volatile and/or nonvolatile memory, such asread only memory (ROM) 431 and/or random access memory (RAM) 432. Thesystem memory RAM 432 may include other dynamic storage device(s) (e.g.,dynamic RAM, static RAM, and synchronous DRAM). The system memory ROM431 may include other static storage device(s) (e.g., programmable ROM,erasable PROM, and electrically erasable PROM). In addition, the systemmemory 430 may be used for storing temporary variables or otherintermediate information during the execution of instructions by theprocessors 420. A basic input/output system (BIOS) 433 containing thebasic routines that help to transfer information between elements withincomputer system 410, such as during start-up, may be stored in ROM 431.RAM 432 may contain data and/or program modules that are immediatelyaccessible to and/or presently being operated on by the processors 420.System memory 430 may additionally include, for example, operatingsystem 434, application programs 435, other program modules 436 andprogram data 437.

The computer system 410 also includes a disk controller 440 coupled tothe bus 421 to control one or more storage devices for storinginformation and instructions, such as a hard disk 441 and a removablemedia drive 442 (e.g., floppy disk drive, compact disc drive, tapedrive, and/or solid state drive). The storage devices may be added tothe computer system 410 using an appropriate device interface (e.g., asmall computer system interface (SCSI), integrated device electronics(IDE), Universal Serial Bus (USB), or FireWire).

The computer system 410 may also include a display controller 465coupled to the bus 421 to control a display 466, such as a cathode raytube (CRT) or liquid crystal display (LCD), for displaying informationto a computer user. The computer system includes an input interface 460and one or more input devices, such as a keyboard 462 and a pointingdevice 461, for interacting with a computer user and providinginformation to the processor 420. The pointing device 461, for example,may be a mouse, a trackball, or a pointing stick for communicatingdirection information and command selections to the processor 420 andfor controlling cursor movement on the display 466. The display 466 mayprovide a touch screen interface which allows input to supplement orreplace the communication of direction information and commandselections by the pointing device 461.

The computer system 410 may perform a portion or all of the processingsteps of embodiments of the invention in response to the processors 420executing one or more sequences of one or more instructions contained ina memory, such as the system memory 430. Such instructions may be readinto the system memory 430 from another computer readable medium, suchas a hard disk 441 or a removable media drive 442. The hard disk 441 maycontain one or more datastores and data files used by embodiments of thepresent invention. Datastore contents and data files may be encrypted toimprove security. The processors 420 may also be employed in amulti-processing arrangement to execute the one or more sequences ofinstructions contained in system memory 430. In alternative embodiments,hard-wired circuitry may be used in place of or in combination withsoftware instructions. Thus, embodiments are not limited to any specificcombination of hardware circuitry and software.

As stated above, the computer system 410 may include at least onecomputer readable medium or memory for holding instructions programmedaccording to embodiments of the invention and for containing datastructures, tables, records, or other data described herein. The term“computer readable medium” as used herein refers to any medium thatparticipates in providing instructions to the processor 420 forexecution. A computer readable medium may take many forms including, butnot limited to, non-volatile media, volatile media, and transmissionmedia. Non-limiting examples of non-volatile media include opticaldisks, solid state drives, magnetic disks, and magneto-optical disks,such as hard disk 441 or removable media drive 442. Non-limitingexamples of volatile media include dynamic memory, such as system memory430. Non-limiting examples of transmission media include coaxial cables,copper wire, and fiber optics, including the wires that make up the bus421. Transmission media may also take the form of acoustic or lightwaves, such as those generated during radio wave and infrared datacommunications.

The computing environment 400 may further include the computer system410 operating in a networked environment using logical connections toone or more remote computers, such as remote computer 480. Remotecomputer 480 may be a personal computer (laptop or desktop), a mobiledevice, a server, a router, a network PC, a peer device or other commonnetwork node, and typically includes many or all of the elementsdescribed above relative to computer system 410. When used in anetworking environment, computer system 410 may include modem 472 forestablishing communications over a network 471, such as the Internet.Modem 472 may be connected to bus 421 via user network interface 470, orvia another appropriate mechanism.

Network 471 may be any network or system generally known in the art,including the Internet, an intranet, a local area network (LAN), a widearea network (WAN), a metropolitan area network (MAN), a directconnection or series of connections, a cellular telephone network, orany other network or medium capable of facilitating communicationbetween computer system 410 and other computers (e.g., remote computer480). The network 471 may be wired, wireless or a combination thereof.Wired connections may be implemented using Ethernet, Universal SerialBus (USB), RJ-11 or any other wired connection generally known in theart. Wireless connections may be implemented using Wi-Fi, WiMAX, andBluetooth, infrared, cellular networks, satellite or any other wirelessconnection methodology generally known in the art. Additionally, severalnetworks may work alone or in communication with each other tofacilitate communication in the network 471.

The embodiments of the present disclosure may be implemented with anycombination of hardware and software. In addition, the embodiments ofthe present disclosure may be included in an article of manufacture(e.g., one or more computer program products) having, for example,computer-readable, non-transitory media. The media has embodied therein,for instance, computer readable program code for providing andfacilitating the mechanisms of the embodiments of the presentdisclosure. The article of manufacture can be included as part of acomputer system or sold separately.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

An executable application, as used herein, comprises code or machinereadable instructions for conditioning the processor to implementpredetermined functions, such as those of an operating system, a contextdata acquisition system or other information processing system, forexample, in response to user command or input. An executable procedureis a segment of code or machine readable instruction, sub-routine, orother distinct section of code or portion of an executable applicationfor performing one or more particular processes. These processes mayinclude receiving input data and/or parameters, performing operations onreceived input data and/or performing functions in response to receivedinput parameters, and providing resulting output data and/or parameters.

A graphical user interface (GUI), as used herein, comprises one or moredisplay images, generated by a display processor and enabling userinteraction with a processor or other device and associated dataacquisition and processing functions. The GUI also includes anexecutable procedure or executable application. The executable procedureor executable application conditions the display processor to generatesignals representing the GUI display images. These signals are suppliedto a display device which displays the image for viewing by the user.The processor, under control of an executable procedure or executableapplication, manipulates the GUI display images in response to signalsreceived from the input devices. In this way, the user may interact withthe display image using the input devices, enabling user interactionwith the processor or other device.

The functions and process steps herein may be performed automatically orwholly or partially in response to user command. An activity (includinga step) performed automatically is performed in response to one or moreexecutable instructions or device operation without user directinitiation of the activity.

The system and processes of the figures are not exclusive. Othersystems, processes and menus may be derived in accordance with theprinciples of the invention to accomplish the same objectives. Althoughthis invention has been described with reference to particularembodiments, it is to be understood that the embodiments and variationsshown and described herein are for illustration purposes only.Modifications to the current design may be implemented by those skilledin the art, without departing from the scope of the invention. Asdescribed herein, the various systems, subsystems, agents, managers andprocesses can be implemented using hardware components, softwarecomponents, and/or combinations thereof. No claim element herein is tobe construed under the provisions of 35 U.S.C. 112, sixth paragraph,unless the element is expressly recited using the phrase “means for.”

1-20. (canceled)
 21. A method for generating a personalized scaffold foran individual, the method comprising: acquiring images of an anatomy ofinterest corresponding to an intended scaffold location; acquiring testresults related to the anatomy of interest; generating one or morefunctional specifications based on the images and test results;selecting one or more scaffold parameters based on the one or morefunctional specifications; generating a final scaffold using the one ormore scaffold parameters.
 22. The method of claim 21, wherein the one ormore functional specifications comprise one or more computational modelparameters.
 23. The method of claim 22, wherein the one or morecomputational model parameters comprise an indication of geometricalfeatures of the anatomy of interest.
 24. The method of claim 22, whereinthe one or more computational model parameters comprise an indication ofmechanical properties in the anatomy of interest.
 25. The method ofclaim 21, wherein the one or more functional specifications comprise oneor more clinical parameters.
 26. The method of claim 25, wherein the oneor more clinical parameters comprise one or more of a diameter, ejectionfraction, flow, or volume corresponding to the anatomy of interest. 27.The method of claim 21, wherein the one or more scaffold parameters areselected based on the one or more functional specifications by a processcomprising: selecting an initial set of scaffold parameters from adatabase based on the one or more functional specifications; optimizingthe initial set of scaffold parameters using a functional computationalmodel to yield the one or more functional specifications.
 28. The methodof claim 21, wherein the final scaffold is generated using the one ormore scaffold parameters using an additive manufacturing process. 29.The method of claim 28, wherein the additive manufacturing processcomprises generating a stereolithography (STL) tetrahedral model withmaterial properties for each tetrahedral corresponding to the one ormore scaffold parameters.
 30. The method of claim 21, wherein the finalscaffold is generated using the one or more scaffold parameters by aprocess comprising: generating a mold based on the one or more scaffoldparameters; and using the mold to grow the final scaffold.
 31. Themethod of claim 21, wherein one or more scaffold parameters comprise aset of optimal printer parameters and generating the final scaffoldusing the one or more scaffold parameters comprises: identifying amapping function which describes a relationship between the one or morefunctional specifications and printer parameters corresponding to athree-dimensional printer; selecting one or more desired outputcharacteristics; generating the set of optimal printer parameters byoptimizing the mapping function according to the one or more desiredoutput characteristics; and using the three-dimensional printer to printa personalized organ according to the set of optimal printer parameters.32. A method for generating a personalized scaffold for an individual,the method comprising: generating one or more functional specificationsbased on images of an anatomy of interest corresponding to an intendedscaffold location and test results related to the anatomy of interest;selecting an initial set of scaffold parameters based on the one or morefunctional specifications; optimizing the initial set of scaffoldparameters using a functional computational model to yield the one ormore functional specifications; and generating a final scaffold usingthe one or more scaffold parameters.
 33. The method of claim 32, whereinthe one or more functional specifications comprise one or morecomputational model parameters.
 34. The method of claim 33, wherein theone or more computational model parameters comprise an indication ofgeometrical features of the anatomy of interest.
 35. The method of claim33, wherein the one or more computational model parameters comprise anindication of mechanical properties in the anatomy of interest.
 36. Themethod of claim 32, wherein the one or more functional specificationscomprise one or more clinical parameters.
 37. The method of claim 36,wherein the one or more clinical parameters comprise one or more of adiameter, ejection fraction, flow, or volume corresponding to theanatomy of interest.
 38. The method of claim 32, wherein the finalscaffold is generated using the one or more scaffold parameters using anadditive manufacturing process.
 39. The method of claim 38, wherein theadditive manufacturing process comprises generating a stereolithography(STL) tetrahedral model with material properties for each tetrahedralcorresponding to the one or more scaffold parameters.
 40. The method ofclaim 32, wherein the final scaffold is generated using the one or morescaffold parameters by a process comprising: generating a mold based onthe one or more scaffold parameters; and using the mold to grow thefinal scaffold.
 41. A system for generating a scaffold for apersonalized regenerative medicine device, the system comprising: animaging device configured to acquire images of an anatomy of interestcorresponding to an intended usage location of the personalizedregenerative medicine device; a processing computer configured to:generate one or more functional specifications based on the images of ananatomy of interest and test results related to the anatomy of interest;select an initial set of scaffold parameters based on the one or morefunctional specifications; optimize the initial set of scaffoldparameters using a functional computational model to yield the one ormore functional specifications; and generate a final scaffold using theone or more scaffold parameters.